浅析单克隆抗体诱导的细胞因子释放综合征  

Preliminary analysis of cytokine-release syndrome induced by monoclonal antibodies

作　　者：林志[1,2] 吕建军[1] 屈哲[1] 耿兴超[1] 杨艳伟[1] 张頔[1] 李珊珊[1] 李波[1] 

机构地区：[1]中国食品药品检定研究院,北京100050 [2]北京中医药大学,北京100029

出　　处：《中国新药杂志》2012年第7期746-750,756,共6页Chinese Journal of New Drugs

基　　金：国家重大新药创制科技重大专项药物安全评价技术平台(2012ZX09302001)

摘　　要：单克隆抗体由于靶向性强、特异性高和毒副作用低等特点,成为近年来复合性增长最快的一类生物技术药物。然而,2006年单克隆抗体TGN1412因为诱发了细胞因子释放综合征(cytokine-release syn-drome,CRS),在I期临床试验中造成了灾难性的后果。由于动物与人存在差异,通过临床前动物实验预测单克隆抗体是否会在人体中造成CRS目前仍存在一定的困难。本文从CRS的定义、安全性法规、发生机制、临床前研究等方面对单克隆抗体所诱导的细胞因子释放综合征进行综述,以探讨如何进行单克隆抗体的CRS临床前风险评估。Monoclonal antibodies（mAbs） are obviously increased with the development of new biotechnological drugs because they are strong targeting,high specificity and low toxicity.However,in 2006,a catastrophic event of the monoclonal antibody TGN1412 in phase I clinical trail occurred as it induced cytokine-release syndrome（CRS）.It is still difficult to predict CRS induced by monoclonal antibody in preclinical toxicity study due to the differences between the animals and human.Here,we discussed the definition of CRS,the guideline for CRS,putative mechanism,and preclinical safety study,so that we could predict CRS in preclinical toxicity study in the future.

关 键 词：单克隆抗体 细胞因子释放综合征 临床前研究 TGN1412 安全性评价 

分 类 号：R963[医药卫生—微生物与生化药学]